Project Summary/Abstract Skin cancer is the most common form of cancer. Each year in the U.S. alone over 5.4 million cases of nonmelanoma skin cancer are treated. The annual cost of treating skin cancers in the U.S. is estimated at $8.1 billion. Treatment and prevention of skin cancer is a significant health care challenge. Physical Sciences Inc. (PSI), in collaboration with Dartmouth College and Cleveland Clinic, proposes to develop a novel optical dosimetry technology and demonstrate its applications in two areas, i.e., real-time measurement of photosensitizer (PS) and singlet oxygen (O2) during photodynamic therapy (PDT), and non-invasive quantification of singlet O2 produced in skin under UV irradiation. This ultrasensitive, robust dosimeter is based on an innovative ?computational spectroscopy? technology and a low-cost hardware configuration. We propose to demonstrate the capability of the singlet O2 dosimeter to guide optimization of PDT protocols for improved skin cancer treatment, as well as to support biomedical research focused on understanding skin damage/carcinogenesis by solar UV irradiation with a goal of accelerating the development of more effective sunscreen products. PDT is a targeted, minimally invasive treatment option for skin cancer. During PDT, singlet oxygen (O2) is produced and is responsible for the cell destruction. At the present time it is difficult, if not impossible, to predict the response of an individual to PDT. Solar UV irradiation causes direct DNA damage and thus skin carcinogenesis. UV irradiation on the skin also generates reactive oxygen species (ROS) including singlet O2, which also contributes to DNA damage. However, the carcinogenesis of ROS produced by UVA is not well understood, hindering developing more effective sunscreen products that protect against UVA and longer wavelengths. Real-time quantification of singlet O2 will benefit both applications, which, in turn, will lead to advancements in skin cancer therapy and prevention. The overall aim of the proposed Fast Track program is to develop and demonstrate the proposed real-time singlet O2 dosimetry technology. PSI will work with Dartmouth Hitchcock Hospital and Cleveland Clinic to demonstrate its application in both PDT and UV skin damage investigations. Beiersdorf, a major producer of skin care products will participate as a consultant at no cost to the program. Phase I will focus on demonstrating the feasibility of the proposed technology, by developing two prototypes and testing them on small scale in vivo (mice) and ex-vivo (human skin) experiments. During Phase II, the prototypes will be optimized and the improved Gen-2 prototypes will be distributed to three institutes for independent testing during large-scale animal studies and limited human patient testing. Successful completion of these tasks will lead to a noninvasive, robust singlet O2/PS dosimeter that could benefit research and clinical practice for curing and preventing skin cancer.